Autoimmune diseases are virtually unstudied in terms of air pollution. Evidence for silica dust and smoking as causes of incident RA suggest that inhaled particulate or chemical pollution may contribute to RA pathogenesis. The purported biologic mechanisms by which these risk factors cause RA - inflammation, systemic immune effects, and oxidative stress - have also been correlated with air pollution, lending biologic plausibility to a possible association between air pollution and RA. Seasonal fluctuations in rheumatic symptoms further suggest that air pollution may contribute to periodic exacerbation of prevalent RA. We propose to investigate ambient air pollution as a contributor to RA incidence and exacerbation, with a focus on exposure to particulate matter (PM2.5 and PM10). We will pursue our aims within the "Border Air Quality Strategy" (BAQS) cohort study of cardiovascular diseases in the Georgia Air Basin of British Columbia (BC). This cohort was enumerated using registration records in the BC Linked Health Database, and includes 870,041 adults, ages 45-84, who had lived in the region for five years before 1999. Air pollutant exposures were assigned to each subject by their individual geographic code(s) of residence, using both air pollution regulatory monitoring networks and land-use regression modeling methods which incorporate both intraurban spatial contrasts and temporal variability. We will follow at-risk subjects at the study baseline (January 1, 1999) to identify RA outcomes during the follow-up period (1999-2003) through searches of ICD9 codes in inpatient and outpatient data. We will investigate the contribution of air pollution exposure on RA incidence using a nested case-control design - comparing average exposure during a 5-year period before RA incidence between cases and matched at-risk controls. We will investigate the contribution of air pollution exposure on RA exacerbation events using a nested case-crossover design - comparing a subject's exposure during a one- month period before the RA exacerbation event to their exposure during selected at-risk periods during which RA exacerbation did not occur. The case-crossover design effectively adjusts for many individual-level risk factors that are not expected to change during the study period. Associations of RA incidence and exacerbation with pollutant levels will be estimated using conditional logistic regression, for our primary pollutants of interest - PM2.5 and PM10. - as well as other air pollutants assessed within the cohort. PUBLIC HEALTH RELEVANCE: Use of the established BAQS cohort, existing health records, and state-of-the-art exposure modeling will provide an efficient means to conduct the first study to date on the potential effects of air pollution on RA - a novel hypothesis that presumably has not been studied previously due to lack of well-characterized, large study populations that are suitable for this purpose. Our proposed study of RA will contribute to a broader understanding of the effects of air pollution in a potentially susceptible population.